A calcium sensing receptor (CaSR) is also called a calcium receptor, and such receptor signals regulate various functions in vivo. Thus, there is a possibility that substances having CaSR agonistic activity are useful for treating or preventing various diseases and also useful as kokumi-imparting agents. Patent Literature 1 discloses a method for screening for a kokumi-imparting substance and a kokumi-imparting agent containing a kokumi-imparting substance obtained by the screening method. In the literature, it is found that various low molecular peptides have CaSR agonistic activity. Based on this finding, it discloses that it becomes possible to provide a kokumi-imparting agent which can impart “kokumi”, the taste that cannot be expressed with five basic tastes of sweetness, saltiness, sourness, bitterness and umami, and the taste that enhances marginal tastes of the basic tastes, such as thickness, growth (mouthfullness), continuity, and harmony.
Meanwhile, it is known that a γ-glutamyl anilide derivative can be used for measuring the enzyme activity since it becomes a substrate of γ-glutamyl transferase (refer to Non-patent Literature 1 and Patent Literature 2). However, there is no reference that discloses the relationship of a γ-glutamyl anilide derivative with “a calcium sensing receptor (CaSR) or a G-protein-coupled receptor”, “kokumi” and “diarrhea or hyperparathyroidism”, each of which is disclosed in the present invention. The main use of some publicly known compounds among 3-sulfonic acid, 3-carboxylic acid and 3-nitro derivatives, each of which are particularly preferable in the present invention, are a substrate in measuring the enzyme activity of γ-glutamyl transferase. As other uses, it is slightly known that it is used as an antimicrobial agent or an antiallergic agent (refer to Non-patent Literature 2 and Patent Literature 3) and as a reagent for mass spectrometry (refer to Non-patent Literature 3). Further, it is known that examples of a compound activating CaSR include cinacalcet and similar synthetic low molecular compounds, and γ-glutamyl peptide derivatives such as glutathione (refer to Patent Literature 4 and Non-patent Literature 4). However, they are structurally different from glutamic acid derivatives of the present invention.
Therefore, it is expected to provide more excellent kokumi-imparting agents by searching more varieties of compounds having CaSR agonistic activity. It is also expected to provide CaSR agonistic agents, pharmaceutical compositions and preventive or therapeutic agents for diarrhea.                Patent Literature 1: WO 2007/055393 A1        Patent Literature 2: U.S. Pat. No. 4,087,331        Patent Literature 3: JP-A 06-172287        Patent Literature 4: WO 2007/055388 A2        Non-patent Literature 1: Clinical Chemistry, 22, 2051 (1976)        Non-patent Literature 2: Journal of Medicinal Chemistry (1965), 8(3), 398-400        Non-patent Literature 3: Analytica Chimica Acta (2004), 519(2), 181-187        Non-patent Literature 4: Journal of Biological Chemistry (2006), 281(13), 8864-70        